Background
As cisplatin (CP) remains one of the most effective antineoplastics used in chemotherapy, strategies to protect tissues against CP toxicity are of clinical interest. A major dose-limiting side effect in CP-based chemotherapy is hepatotoxicity. Remote ischemic preconditioning (rIP) represents a noninvasive model for organ protection. The present study was designed to examine, in vivo, the CP-induced hepatic injury and to find the protective probability of rIP in this model in relation to an inflammatory mechanism and the hepatic energetic activity.
Materials and methods
Twenty-four adult male albino rats were divided equally into three groups that were treated as follows: (i) control group, (ii) CP group (single intraperitoneal injection of CP 7 mg/kg body weight), and (iii) preconditioned group. rIP was induced with three 10-min ischemia/10-min reperfusion cycles of the right hind limbs just before CP injection. The animals were killed 14 days after the treatment. Among all groups, the gene expression of nuclear factor 0κB (NF-κB), coenzyme Q10 (Mito.Q10), an autophagy marker LC3 and fatty acid-binding protein L-FABP was assessed by real-time reverse transcription-PCR in the rat liver tissue, in addition, the serum levels of liver enzymes alanine aminotransferase and aspartate transaminase were measured.
Results
CP induced an increase in hepatic NF-κB and mitochondrial dysfunction as reflected by the decrease in Mito.Q10 and a significant reduction in the mitochondrial clearance mechanism: mitochondrial autophagy, which is known as mitophagy. Further, CP significantly decreased the expression of the main protein involved in fatty acid transport, L-FABP, which is also considered an effective endogenous antioxidant. However, these alterations were ameliorated in preconditioned rats.
Conclusion
We can assume that the alleviative outcome of rIP in CP-induced hepatotoxicity could be because of induction of anti-inflammatory and antioxidant responses associated with the upregulation of mitochondrial function.